Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Development of a perception system for road environment using multiple sources of information

145 σ.Τον τελευταίο καιρό η έρευνα για τον περιορισμό των τροχαίων ατυχημάτων στρέφεται όλο και περισσότερο στην μελέτη της τοποθέτησης και λειτουργίας μιας ευρείας γκάμας αισθητήρων πάνω στα οχήματα. Σκοπός των συστημάτων που αναπτύσσονται είναι η αντίληψη του περιβάλλοντος και η αξιολόγηση της τρέχουσας κατάστασης για την έγκαιρη προειδοποίηση του οδηγού σε κρίσιμες καταστάσεις ή ακόμα και η ανάληψη μερική ή ολική του ελέγχου του οχήματος. Η χρησιμότητα των συστημάτων αυτών έχει ήδη αρχίσει να αναγνωρίζεται και ήδη έχουν αρχίσει να εμφανίζονται τα πρώτα εμπορικά συστήματα σε μεγάλα οχήματα όπως φορτηγά ή αυτοκίνητα πολυτελείας με έναν ή δυο το πολύ αισθητήρες προς το παρών. Οι λειτουργίες που ενσωματώνονται σε αυτές τις εφαρμογές είναι η αποφυγή σύγκρουσης, η πλευρική ασφάλεια, η υποβοήθηση ταχύτητας, η υποβοήθηση σε διασταυρώσεις και η υποβοήθηση σε καταστάσεις παύσης και έναρξης κίνησης. Η χρήση τους αυξάνεται προς το παρών με αργούς ρυθμούς καθώς βρίσκονται στα αρχικά στάδια της μελέτης και ανάπτυξης τους, αλλά προβλέπεται σε μερικά χρόνια να αρχίσει σταδιακά η μαζική χρήση τους. Καθώς η έρευνα προχωράει, η μελέτη στρέφεται στην εγκατάσταση και λειτουργία συστημάτων με πολλαπλούς αισθητήρες οι οποίοι θα καλύπτουν όλη την περιοχή γύρω από το όχημα. Σκοπός είναι η πλήρης αντίληψη όλων των περιοχών εμπρός, πίσω, αριστερά και δεξιά από το αυτοκίνητο για την προστασία από περιπτώσεις όπως π.χ. η σύγκρουση με ένα διπλανό όχημα κατά την αλλαγή λωρίδας ή η σύγκρουση με ένα εμπόδιο μπροστά σε συνθήκες περιορισμένης ορατότητας. Οι αισθητήρες που χρησιμοποιούνται είναι κυρίως μικροκυματικά ραντάρ για την ανίχνευση κινούμενων οχημάτων, κάμερες για την ανίχνευση κυρίως των λωρίδων και των ορίων του δρόμου, σαρωτές laser για την ανίχνευση του δρόμου και άλλων οχημάτων, υπέρυθρες κάμερες για την ανίχνευση αντικειμένων το βράδυ, ψηφιακοί χάρτες για πληροφορίες σχετικά με τον δρόμο, δέκτες GPS για την εύρεση της θέσης και αδρανειακοί αισθητήρες για την εκτίμηση της δυναμικής κατάστασης του οχήματος. Σκοπός της διατριβής είναι η εισαγωγή ορισμένων πρωτότυπων αλγορίθμων όσον αφορά την αποτελεσματική αντίληψη του οδικού περιβάλλοντος σε εφαρμογές υποβοήθησης του οδηγού σε έξυπνα οχήματα και η ανάπτυξη μιας πρωτότυπης πλατφόρμας για την λήψη και επεξεργασία των δεδομένων από τους αισθητήρες με τους οποίους είναι εξοπλισμένο το όχημα. Πιο συγκεκριμένα περιλαμβάνει μια σύντομη εισαγωγή στα συστήματα οδικής ασφάλειας, όπου γίνεται επίσης παρουσίαση της αρχιτεκτονικής του πυρήνα επεξεργασίας των πληροφοριών από τους αισθητήρες κάνοντας χρήση τεχνικών σύντηξης δεδομένων Στη συνέχεια παρουσιάζονται ορισμένοι νέοι αλγόριθμοι και βελτιώνονται ορισμένοι υπάρχοντες σε σχέση με την επεξεργασία των δεδομένων από τους αισθητήρες αυτούς που είναι εγκατεστημένοι πάνω στο όχημα. Το πεδίο στο οποίο εστιάζεται είναι η εκτίμηση της γεωμετρίας του δρόμου με χρήση ψηφιακών χαρτών καθώς και η εκτίμηση της ίδιας γεωμετρίας σε μεταγενέστερο στάδιο με χρήση πολλαπλών πηγών πληροφορίας. Επίσης, αναλύονται οι μέθοδοι αξιολόγησης κατάστασης και ιδιαίτερα αυτοί που αφορούν την εκτίμηση των συντελεστών κινδύνου καθώς και την ανίχνευση των εκτελούμενων ελιγμών και την εξακρίβωση της πρόθεσης του οδηγού. Στο τέλος παρουσιάζεται μια πρότυπη πλατφόρμα η οποία εστιάζει στην πλευρική ασφάλεια.In recent years the on-going research, for decreasing road accidents, focus in using various sensors onboard vehicles for perceiving the road environment. This effort aims in detecting and recognizing the current situation evolving around the vehicle in order to inform or warn the driver or even take control of the vehicle. The importance of such systems has already started being recognized and nowadays the first generation of such systems is equipping heavy trucks or luxurious vehicles by using one or two different sensors. The functions that are developed are collision avoidance, lane keeping, speed assistance, intersection support and stop & go. Currently, their market penetration is very low, as those systems are under research and development, but it is anticipated their extended use in the near future. The main purpose is the field of view of all sensors to include the whole area of the vehicle. Thus, for example, the driver assistance system (ADAS) should be able to cover a possible collision with another vehicle moving in the adjacent lane during a lane change, or the collision with an obstacle in front of the vehicle during bad weather. Typical sensors used in ADAS systems are radars, cameras, laser scanners, infrared cameras, digital maps, GPS and inertial sensors for estimating the vehicle dynamics. This thesis includes a short introduction in advanced driver assistance systems, the presentation of the architecture of data fusion systems and the proposal of some new algorithms or the extension of previous ones for the processing of data provided by the sensor network installed on the vehicle. The main work focuses at the road geometry estimation using digital maps and the lane estimation using multiple sources of information. It is also focusing in the development of algorithms regarding situation assessment and particularly at estimating the risks involved with the current situation. It is also deals with the problem of detecting the performed maneuver by the driver and the intention associated with the corresponding maneuver. Finally, a software platform for testing all the proposed algorithms is developed and presented.Εμμανουήλ Ν. Τσόγκα

In vivo effects of a Ginkgo biloba extract on platelet activating factor metabolism in two asymptomatic HIV-infected patients

Ginkgo biloba products seem to protect from several pathological conditions, including HIV manifestations, where Platelet Activating Factor (PAF) is implicated. In the present study, we examined for the first time the in vivo effects of a standardized formulation of Ginkgo biloba extract (150 mg daily, per os) on PAF metabolism in blood cells and plasma of two male, asymptomatic HIV-infected patients, not receiving antiretroviral treatment, during a 9-month period. These patients differed at baseline in terms of duration of HIV infection, viral load levels, CD4 cell counts and Highly Active Antiretroviral Therapy (HAART) experience. In the first patient with early HIV infection, after an initial transient increase, a return of both plasma viral load and PAF biosynthetic enzyme activities in leukocytes to their baseline levels was observed during Ginkgo biloba use. As a result PAF degradation also remained low in this patient. The second patient with late but not advanced HIV infection, had higher levels of viral load and a lower CD4 cell count at baseline. The use of 150 mg of a Ginkgo biloba extract was probably insufficient to induce PAF degradation and/or to suppress the induction of PAF biosynthesis observed. At the same time, the initial high levels of viral load were further increased and CD4 cell counts were finally decreased during the study. The observed differences in PAF metabolism during Ginkgo use seem to be related to the initial heterogeneity of these patients. It appears that in some HIV-infected patients inhibition of the PAF/PAF-receptor system, along with a decrease/down-regulation of PAF-biosynthesis, illustrates a new potential role for Ginkgo biloba compounds in the treatment of HIV infection and its manifestations. However, more tests on a larger number of patients are needed in order to support these preliminary observations. Copyright © by BIOLIFE, s.a s

Effects of HAART on platelet-activating factor metabolism in naive HIV-infected patients I: Study of the tenofovir-DF/emtricitabine/efavirenz HAART regimen

Platelet-activating factor (PAF) is implicated in human immunodeficiency virus (HIV)-related manifestations. Increased PAF synthesis has been recently detected in HIV-infected patients. In this study, we examined in naive HIV-infected patients the in vivo effects of a highly active antiretroviral therapy (HAART) regimen, containing tenofovir-DF/emtricitabine/efavirenz, on PAF metabolism. The specific activities of PAF basic biosynthetic enzymes, PAF-cholinephosphotransferase (PAF-CPT) and lyso-PAF-acetyltransferase (lyso-PAF-AT), but also the ones of PAF-basic catabolic enzymes, PAF acetylhydrolase (PAF-AH) in leukocytes and platelets, and lipoprotein- associated-phospholipase-A2 (LpPLA2) in plasma, were measured in blood samples of eight asymptomatic naive male HIV-infected patients just before and after 1, 3, and 6 months of treatment. CD4 cell counts, viral load, and several biochemical markers were also measured in the same blood samples of these patients. The repeated measures ANOVA and the Pearson r criterion were used to study statistical differences and correlations-partial correlations, while linear mixed models were conducted in order to estimate association(s) between time-dependent changes in these factors. Before treatment, the activities of PAF-CPT in leukocytes and LpPLA2 in plasma were found to be inversely correlated with CD4 cell counts and positively correlated with the viral load. After 6 months of treatment, the activities of basic PAF-biosynthetic enzymes, PAF-CPT and lyso-PAF-AT, were both reduced in leukocytes. At 6 months, PAF-AH activity was also reduced in these cells, while LpPLA2 remained stable. The reduction of PAF-CPT occurred even from the first month, while there is a time-dependent correlation between the increase of CD4 and the decrease of both viral load and PAF-CPT of leukocytes during treatment. Apart from its classical antiretroviral activities the tenofovir-DF/emtricitabine/efavirenz regimen also exhibited favorable effects on PAF metabolism and therefore may also display beneficial effects in some HIV-related conditions, such as cardiovascular disease (CVD), in which PAF is implicated. © Copyright 2012, Mary Ann Liebert, Inc. 2012